This renewal of AG-05142 proposes an Alzheimer Disease Research Center (ADRC) program seated at USC with 4 aims and 4 new projects. Aim 1: Identify molecular and cellular mechanisms of neurodegeneration during D and normal aging processes. Aim 2: Develop hormonal interventions into age-related cognitive changes with clinical studies and animal models. Aim 3: Develop cognitive & imaging techniques to monitor aging, AD, & clinical interventions. Aim 4: Increase participation of Hispanic, African-American, and other minorities in drug trials. The USC-ADRC is comprised of the required cores and two special-service cores*: Clinical Core: Dir., Victor Henderson; co-Dir. Lon Schneider (Pharmacology Program). Minority Diagnosis and Treatment Satellite*, Dr. Helena Chui. Neuroimaging Core*, Dr. Manbir Singh. Neuropathology Core, Dir. Carol Miller. Education Information Transfer Core, Dir, Bob Knight. These cores serve four new projects of USC faculty: Proj. Alzheimer-like pathology in inclusion-body myopathy (Valerie Askanas). Proj. Choroid plexus in Abeta/apolipoprotein CNS homeostasis (Berislav Zlokovic). Proj. Aberrant DNA synthesis in dividing and non-dividing cells (Myron Goodman). Proj. fMRI studies of working memory, estrogen, & aging (MaryEllen MacDonald and Manbir Singh). The Cores also support a collaborative longitudinal study with Kaiser Permanente: Alzheimer disease & estrogen replacement; Galen Buckwater, co-PI) and two NIA program projects: Models of estrogen interactions with AD and The aging brain: vasculature, ischemia, & behavior. Genotypes of human subjects are obtained through the Molecular Biology Core of the NIEHS enter (John Peters, Dir.) Other users of these resources includes >40 federally funded USC faculty (Schools of Medicine; of Pharmacy; of Gerontology of Letters, Arts, & Sciences; and of Engineering), as well as >20 non-USC researchers. Collaborations with ADRCs of UCLA, UC Irvine, UC San Diego, Boston U, Columbia, Emory, Washington U, U Washington. These approaches to AD build on AD build on USC's long-standing commitment to research and education on aging.